Fenogal General Information

Fenogal - Pharmacology:

Fenogal exerts its therapeutic effects through activation of peroxisome proliferator activated receptor a (PPARa). This increases lipolysis and elimination of triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of apoprotein C-III. The resulting fall in triglycerides produces an alteration in the size and composition of LDL from small, dense particles, to large buoyant particles. These larger particles have a greater affinity for cholesterol receptors and are catabolized rapidly.

Fenogal Interactions

Oral Anticoagulants

CAUTION SHOULD BE EXERCISED WHEN COUMARIN ANTICOAGULANTS ARE GIVEN IN CONJUNCTION WITH TRICOR. THE
DOSAGE OF THE ANTICOAGULANTS SHOULD BE REDUCED TO MAINTAIN THE PROTHROMBIN TIME/INR AT THE DESIRED LEVEL TO PREVENT
BLEEDING COMPLICATIONS. FREQUENT PROTHROMBIN TIME/INR DETERMINATIONS ARE ADVISABLE UNTIL IT HAS BEEN DEFINITELY
DETERMINED THAT THE PROTHROMBIN TIME/INR HAS STABILIZED.

HMG-CoA reductase inhibitors

The combined use of TRICOR and HMG-CoA reductase inhibitors should be avoided unless the benefit of further
alterations in lipid levels is likely to outweigh the increased risk of this drug combination.

Resins

Since bile acid sequestrants may bind other drugs given concurrently, patients should take TRICOR at least 1 hour
before or 4-6 hours after a bile acid binding resin to avoid impeding its absorption.

Cyclosporine

Because cyclosporine can produce nephrotoxicity with decreases in creatinine clearance and rises in serum
creatinine, and because renal excretion is the primary elimination route of fibrate drugs including TRICOR, there is
a risk that an interaction will lead to deterioration. The benefits and risks of using TRICOR with immunosuppressants
and other potentially nephrotoxic agents should be carefully considered, and the lowest effective dose employed.

Drug-drug interactions

In vitro studies using human liver microsomes indicate that fenofibrate and fenofibric acid are not
inhibitors of cytochrome (CYP) P450 isoforms CYP3A4, CYP2D6, CYP2E1, or CYP1A2. They are weak inhibitors of CYP2C19
and CYP2A6, and mild-to-moderate inhibitors of CYP2C9 at therapeutic concentrations.

Potentiation of coumarin-type anticoagulants has been observed with prolongation of the prothrombin time/INR.

Bile acid sequestrants have been shown to bind other drugs given concurrently. Therefore, fenofibrate should be
taken at least 1 hour before or 4-6 hours after a bile acid binding resin to avoid impeding its absorption .

Concomitant administration of fenofibrate (equivalent to 145mg TRICOR) with pravastatin (40 mg) once daily for 10
days has been shown to increase the mean Cmax and AUC values for pravastatin by 36% (range from 69%
decrease to 321% increase) and 28% (range from 54% decrease to 128% increase), respectively, and for
3α-hydroxy-iso-pravastatin by 55% (range from 32% decrease to 314% increase) and 39% (range from 24% decrease
to 261% increase), respectively in 23 healthy adults.

A single dose of pravastatin had no clinically important effect on the pharmacokinetics of fenofibric acid.

Concomitant administration of fenofibrate (equivalent to 145 mg TRICOR) with atorvastatin (20 mg) once daily for
10 days resulted in approximately 17% decrease (range from 67% decrease to 44% increase) in atorvastatin AUC values
in 22 healthy males. The atorvastatin Cmax values were not significantly affected by fenofibrate. The
pharmacokinetics of fenofibric acid were not significantly affected by atorvastatin.

Fenogal Contraindications

TRICOR is contraindicated in patients who exhibit hypersensitivity to fenofibrate.

TRICOR is contraindicated in patients with hepatic or severe renal dysfunction, including primary
biliary cirrhosis, and patients with unexplained persistent liver function abnormality.

TRICOR is contraindicated in patients with preexisting gallbladder disease.